tbuckley/cabot-search huggingface dataset:
Genome-by-Trauma Exposure Interactions in Adults With Depression in the UK Biobank
Authors: Melisa Chuong, Mark J. Adams, Alex S. F. Kwong, Chris S. Haley, Carmen Amador, Andrew M. McIntosh
Journal: JAMA Psychiatry (2022)

Importance Self-reported trauma exposure has consistently been found to be a risk factor for major depressive disorder (MDD), and several studies have reported interactions with genetic liability. To date, most studies have examined gene-environment interactions with trauma exposure using genome-wide variants (single-nucleotide variations [SNVs]) or polygenic scores, both typically capturing less than 3% of phenotypic risk variance. Objective To reexamine genome-by-trauma interaction associations using genetic measures using all available genotyped data and thus, maximizing accounted variance. Design, Setting, and Participants The UK Biobank study was conducted from April 2007 to May 1, 2016 (follow-up mental health questionnaire). The current study used available cross-sectional genomic and trauma exposure data from UK Biobank. Participants who completed the mental health questionnaire and had available genetic, trauma experience, depressive symptoms, and/or neuroticism information were included. Data were analyzed from April 1 to August 30, 2021. Exposures Trauma and genome-by-trauma exposure interactions. Main Outcomes and Measures Measures of self-reported depression, neuroticism, and trauma exposure with whole-genome SNV data are available from the UK Biobank study. Here, a mixed-model statistical approach using genetic, trauma exposure, and genome-by-trauma exposure interaction similarity matrices was used to explore sources of variation in depression and neuroticism. Results Analyses were conducted on 148 129 participants (mean [SD] age, 56 [7] years) of which 76 995 were female (52.0%). The study approach estimated the heritability (SE) of MDD to be approximately 0.160 (0.016). Subtypes of self-reported trauma exposure (catastrophic, adult, childhood, and full trauma) accounted for a significant proportion of the variance of MDD, with heritability (SE) ranging from 0.056 (0.013) to 0.176 (0.025). The proportion of MDD risk variance accounted for by significant genome-by-trauma interaction revealed estimates (SD) ranging from 0.074 (0.006) to 0.201 (0.009). Results from sex-specific analyses found genome-by-trauma interaction variance estimates approximately 5-fold greater for MDD in male participants (0.441 [0.018]) than in female participants (0.086 [0.009]). Conclusions and Relevance This cross-sectional study used an approach combining all genome-wide SNV data when exploring genome-by-trauma interactions in individuals with MDD; findings suggest that such interactions were associated with depression manifestation. Genome-by-trauma interaction accounts for greater trait variance in male individuals, which points to potential differences in depression etiology between the sexes. The methodology used in this study can be extrapolated to other environmental factors to identify modifiable risk environments and at-risk groups to target with interventions.
To Disclose or Not to Disclose: Secondary Findings of XXY Chromosomes
Authors: Benjamin S. Wilfond, Devan M. Duenas, Liza-Marie Johnson
Journal: The American Journal of Bioethics (2022)

"To Disclose or Not to Disclose: Secondary Findings of XXY Chromosomes." The American Journal of Bioethics, 22(10), pp. 87–88
Change to Open Access Status
Authors: Peter Barr, Tim Bigdeli, Jacquelyn Meyers
Journal: JAMA Psychiatry (2022)

Siwen Wang, MD; Luwei Quan, BA; Jorge E. Chavarro, ScD; Natalie Slopen, ScD; Laura D. Kubzansky, PhD; Karestan C. Koenen, PhD; Jae Hee Kang, ScD; Marc G. Weisskopf, PhD; Westyn Branch-Elliman, MD; Andrea L. Roberts, PhD
Neoadjuvant Chemoradiation Therapy for All Elderly Patients With Locally Advanced Rectal Cancer?
Authors: José G. Guillem, William Y. Luo, Chris B. Agala
Journal: JAMA Surgery (2022)

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Considering the Future of Pediatric Multiple Sclerosis Trials After the CONNECT Open-Label Randomized Trial
Authors: Omar Abdel-Mannan, Olga Ciccarelli, Yael Hacohen
Journal: JAMA Network Open (2022)

Patrick Vermersch, MD, PhD; Matthew Scaramozza, MS; Seth Levin, MD; Raed Alroughani, MD; Kumaran Deiva, MD, PhD; Carlo Pozzilli, MD, PhD; Jennifer Lyons, MD; Oksana Mokliatchouk, PhD; Joe Pultz, PhD; Fatou N'Dure, MBA; Shifang Liu, PhD; Runda Badwan, PharmD; Filipe Branco, MSc; Valencia Hood-Humphrey, MS; Nathalie Franchimont, MD, PhD; Jerome Hanna, MBBCh, BAO; Amir-Hadi Maghzi, MD
Within-City Variation in Ambient Carbon Monoxide Concentrations: Leveraging Low-Cost Monitors in a Spatiotemporal Modeling Framework
Authors: Jianzhao Bi, Christopher Zuidema, David Clausen, Kipruto Kirwa, Michael T. Young, Amanda J. Gassett, Edmund Y. W. Seto, Paul D. Sampson, Timothy V. Larson, Adam A. Szpiro, Lianne Sheppard, Joel D. Kaufman
Journal: Environmental Health Perspectives (2022)

Background: Based on human and animal experimental studies, exposure to ambient carbon monoxide (CO) may be associated with cardiovascular disease outcomes, but epidemiological evidence of this link is limited. The number and distribution of ground-level regulatory agency monitors are insufficient to characterize fine-scale variations in CO concentrations. Objectives: To develop a daily, high-resolution ambient CO exposure prediction model at the city scale. Methods: We developed a CO prediction model in Baltimore, Maryland, based on a spatiotemporal statistical algorithm with regulatory agency monitoring data and measurements from calibrated low-cost gas monitors. We also evaluated the contribution of three novel parameters to model performance: high-resolution meteorological data, satellite remote sensing data, and copollutant (PM2.5, NO2, and NOx) concentrations. Results: The CO model had spatial cross-validation (CV) R2 and root-mean-square error (RMSE) of 0.70 and 0.02 parts per million (ppm), respectively; the model had temporal CV R2 and RMSE of 0.61 and 0.04 ppm, respectively. The predictions revealed spatially resolved CO hot spots associated with population, traffic, and other nonroad emission sources (e.g., railroads and airport), as well as sharp concentration decreases within short distances from primary roads. Discussion: The three novel parameters did not substantially improve model performance, suggesting that, on its own, our spatiotemporal modeling framework based on geographic features was reliable and robust. As low-cost air monitors become increasingly available, this approach to CO concentration modeling can be generalized to resource-restricted environments to facilitate comprehensive epidemiological research. https://doi.org/10.1289/EHP10889
The Perspective of Value in Caring for Critically Ill Patients—Is It All About the Benjamins?
Authors: Evie Marcolini, Brian T. Wessman
Journal: JAMA Network Open (2022)

The business of medicine is governed by economic principles balancing supply and demand. What are the implications when something intrinsically valuable, such as health care, is a part of the equation? How does a consumer or a researcher define the economic value of an intervention?
Early vs Late Surgical Decompression for Central Cord Syndrome
Authors: Jetan H. Badhiwala, Jefferson R. Wilson, James S. Harrop, Alexander R. Vaccaro, Bizhan Aarabi, Fred H. Geisler, Michael G. Fehlings
Journal: JAMA Surgery (2022)

Importance The optimal clinical management of central cord syndrome (CCS) remains unclear; yet this is becoming an increasingly relevant public health problem in the face of an aging population. Objective To provide a head-to-head comparison of the neurologic and functional outcomes of early (&amp;amp;lt;24 hours) vs late (≥24 hours) surgical decompression for CCS. Design, Setting, and Participants Patients who underwent surgery for CCS (lower extremity motor score [LEMS] − upper extremity motor score [UEMS] ≥ 5) were included in this propensity score–matched cohort study. Data were collected from December 1991 to March 2017, and the analysis was performed from March 2020 to January 2021. This study identified patients with CCS from 3 international multicenter studies with data on the timing of surgical decompression in spinal cord injury. Participants were included if they had a documented baseline neurologic examination performed within 14 days of injury. Participants were eligible if they underwent surgical decompression for CCS. Exposures Early surgery was compared with late surgery. Main Outcomes and Measures Propensity scores were calculated as the probability of undergoing early compared with late surgery using the logit method and adjusting for relevant confounders. Propensity score matching was performed in a 1:1 ratio by an optimal-matching technique. The primary end point was motor recovery (UEMS, LEMS, American Spinal Injury Association [ASIA] motor score [AMS]) at 1 year. Secondary end points were Functional Independence Measure (FIM) motor score and complete independence in each FIM motor domain at 1 year. Results The final study cohort consisted of 186 patients with CCS. The early-surgery group included 93 patients (mean [SD] age, 47.8 [16.8] years; 66 male [71.0%]), and the late-surgery group included 93 patients (mean [SD] age, 48.0 [15.5] years; 75 male [80.6%]). Early surgical decompression resulted in significantly improved recovery in upper limb (mean difference [MD], 2.3; 95% CI, 0-4.5; P = .047), but not lower limb (MD, 1.1; 95% CI, −0.8 to 3.0; P = .30), motor function. In an a priori–planned subgroup analysis, outcomes were comparable with early or late decompressive surgery in patients with ASIA Impairment Scale (AIS) grade D injury. However, in patients with AIS grade C injury, early surgery resulted in significantly greater recovery in overall motor score (MD, 9.5; 95% CI, 0.5-18.4; P = .04), owing to gains in both upper and lower limb motor function. Conclusions and Relevance This cohort study found early surgical decompression to be associated with improved recovery in upper limb motor function at 1 year in patients with CCS. Treatment paradigms for CCS should be redefined to encompass early surgical decompression as a neuroprotective therapy.
Contrasting Case-Control and Normative Reference Approaches to Capture Clinically Relevant Structural Brain Abnormalities in Patients With First-Episode Psychosis Who Are Antipsychotic Naive
Authors: Natalie Remiszewski, James Edward Bryant, Saige E. Rutherford, Andre F. Marquand, Eric Nelson, Ibrahim Askar, Adrienne Carol Lahti, Nina Vanessa Kraguljac
Journal: JAMA Psychiatry (2022)

To make progress toward precision psychiatry, it is crucial to move beyond case-control studies and instead capture individual variations and interpret them in the context of a normal range of biological systems.To evaluate whether baseline deviations from a normative reference range in subcortical volumes are better predictors of antipsychotic treatment response than raw volumes in patients with first-episode psychosis (FEP) who were naive to antipsychotic medication.In this prospective longitudinal study, patients with first-episode psychosis who were referred from different clinical settings (emergency department, inpatient units, and outpatient clinics) at the University of Alabama at Birmingham were included. A total of 286 patients were screened, 114 consented, 104 enrolled in the treatment trial, and 85 completed the trial. Patients were observed for 16 weeks. Controls were matched by age and sex. Data were collected between June 2016 and July 2021, and data were analyzed from August 2021 to June 2022.Risperidone on a flexible dosing scheme for 16 weeks. There was an option to switch to aripiprazole for excessive adverse effects.The main outcome of this study was to evaluate, in patients with FEP who were naive to antipsychotic medication, the association of baseline raw volumes and volume deviations in subcortical brain regions with response to antipsychotic medication. Raw brain volumes or volume deviation changes after treatment were not examined.Of 190 included participants, 111 (58.4%) were male, and the mean (SD) age was 23.7 (5.5) years. Volumes and deviations were quantified in 98 patients with FEP, and data from 92 controls were used as comparison for case-control contrasts and reference curve calibration. In case-control contrasts, patients with FEP had lower raw thalamus (P = .002; F = 9.63; df = 1), hippocampus (P = .009; F = 17.23; df = 1), amygdala (P = .01; F = 6.55; df = 1), ventral diencephalon (P = .03; F = 4.84; df = 1), and brainstem volumes (P = .004; F = 8.39; df = 1). Of 98 patients, 36 patients with FEP (36%) displayed extreme deviations. Associations with treatment response significantly differed between raw volume and deviation measures in the caudate (z = -2.17; P = .03) and putamen (z = -2.15; P = .03).These data suggest that normative modeling allows capture of interindividual heterogeneity of regional brain volumes in patients with FEP and characterize structural pathology in a clinically relevant fashion. This holds promise for progress in precision medicine in psychiatry, where group-level studies have failed to derive reliable maps of structural pathology.
Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression
Authors: Hugo Bottemanne, Orphee Morlaas, Anne Claret, Tali Sharot, Philippe Fossati, Liane Schmidt
Journal: JAMA Psychiatry (2022)

Importance Clinical research has shown that persistent negative beliefs maintain depression and that subanesthetic ketamine infusions induce rapid antidepressant responses. Objective To evaluate whether ketamine alters belief updating and how such cognitive effects are associated with the clinical effects of ketamine. Design, Setting, and Participants This study used an observational case-control protocol with a mixed-effects design that nested 2 groups by 2 testing time points. Observers were not blinded. Patients with treatment-resistant depression (TRD) and healthy volunteer participants aged 34 to 68 years were included. Patients with TRD were diagnosed with major depressive disorder or bipolar depression, had a Montgomery-Åsberg Depression Rating Scale score greater than 20, a Maudsley Staging Method score greater than 7, and failed to respond to at least 2 prior antidepressant trials. Exclusion criteria were any other psychiatric, neurological, or neurosurgical comorbidities, substance use or addictive disorders, and recreational ketamine consumption. Data were collected from January to February 2019 and from May to December 2019, and data were analyzed from January 2020 to July 2021. Exposures Patients with TRD were observed 24 hours before single ketamine infusion, 4 hours after the infusion, and 4 hours after the third infusion, which was 1 week after the first infusion. Healthy control participants were observed twice 1 week apart without ketamine exposure. Main Outcomes and Measures Montgomery-Åsberg Depression Rating Scale score and belief updating after belief updating when patients received good news and bad news measured by a cognitive belief-updating task and mathematically formalized by a computational reinforcement learning model. Results Of 56 included participants, 29 (52%) were male, and the mean (SEM) age was 52.3 (1.2) years. A total of 26 patients with TRD and 30 control participants were included. A significant group × testing time point × news valence interaction showed that patients with TRD updated their beliefs more after good than bad news following a single ketamine infusion (controlled for age and education: β = −0.91; 95% CI, −1.58 to −0.24; t 216 = −2.67; P = .008) than controls. Computational modeling showed that this effect was associated with asymmetrical learning rates (LRs) after ketamine treatment (good news LRs after ketamine, 0.51 [SEM, 0.04]; bad news LRs after ketamine 0.36 [SEM, 0.03], t 25 = 3.8; P &amp;amp;lt; .001) and partially mediated early antidepressant responses (path a*b : β = −1.00 [SEM, 0.66]; t 26 = −1.53; z = −1.98; P = .04). Conclusions and Relevance These findings provide novel insights into the cognitive mechanisms of the action of ketamine in patients with TRD, with promising perspectives for augmented psychotherapy for individuals with mood disorders.
Assessment of Medical Industry Compensation to US Physicians by Gender
Authors: Brittany G. Sullivan, Fares Al-Khouja, Margaret Herre, Morgan Manasa, Alexander Kreger, Jessica Escobar, Andreea Dinicu, Ariana Naaseh, Farideh Dehkordi-Vakil, Michael Stamos, Alessio Pigazzi, Mehraneh D. Jafari
Journal: JAMA Surgery (2022)

It has been well established that female physicians earn less than their male counterparts in all specialties and ranks despite controlling for confounding variables.To investigate payments made from highest-grossing medical industry companies to female and male physicians and to assess compensation and engagement disparities based on gender.This retrospective, population-based cross-sectional study used data from the Open Payments database for the 5 female and 5 male physicians who received the most financial compensation from each of the 15 highest-grossing medical supply companies in the US from January 2013 to January 2019.The primary outcome was total general payments received by female and male physicians from medical industry over time and across industries. The secondary outcome was trends in industry payment to female and male physicians from 2013 to 2019.Among the 1050 payments sampled, 1017 (96.9%) of the 5 highest earners were men and 33 (3.1%) were women. Female physicians were paid a mean (SD) of $41 320 ($88 695), and male physicians were paid a mean (SD) of $1 226 377 ($3 377 957) (P < .001). On multivariate analysis, male gender was significantly associated with higher payment after adjusting for rank, h-index, and specialty (mean [SD], $1 025 413 [$162 578]; P < .001). From 2013 to 2019, the payment gap between female and male physicians increased from $54 343 to $166 778 (P < .001).This study found that male physicians received significantly higher payments from the highest-grossing medical industry companies compared with female physicians. This disparity persisted across all medical specialties and academic ranks. The health care industry gender payment gap continued to increase from 2013 to 2019, with a wider compensation gap in 2019.
Vitamin D Status, Vitamin D Receptor Polymorphisms, and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes: A Prospective Study
Authors: Xue Chen, Zhenzhen Wan, Tingting Geng, Kai Zhu, Rui Li, Qi Lu, Xiaoyu Lin, Sen Liu, Liangkai Chen, Yanjun Guo, Zhilei Shan, Liegang Liu, An Pan, JoAnn E. Manson, Gang Liu
Journal: Diabetes Care (2022)

OBJECTIVE Evidence is limited regarding the associations between vitamin D status and microvascular complications in individuals with type 2 diabetes (T2D), among whom vitamin D deficiency or insufficiency is particularly common. In this study we aimed to prospectively investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] and vitamin D receptor (VDR) polymorphisms with risk of diabetic microvascular complications. RESEARCH DESIGN AND METHODS This analysis included 14,709 participants with T2D who were free of microvascular complications from the UK Biobank. Incidence of diabetic microvascular complications was ascertained via electronic health records. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS Median serum 25(OH)D concentration was 40.7 nmol/L (interquartile range 27.5, 56.4). During a median of 11.2 years of follow-up, 1,370 people developed diabetic microvascular complications. Compared with participants with 25(OH)D &amp;lt;25 nmol/L, individuals with 25(OH)D ≥75 nmol/L had a multivariable-adjusted HR of 0.65 (95% CI 0.51, 0.84) for composite diabetic microvascular complications, 0.62 (0.40, 0.95) for diabetic retinopathy, 0.56 (0.40, 0.79) for diabetic nephropathy, and 0.48 (0.26, 0.89) for diabetic neuropathy. In addition, in comparisons with participants with 25(OH)D &amp;lt;25 nmol/L and minor allele homozygotes (TT of rs1544410 and GG of rs731236), the multivariable-adjusted HRs of composite diabetic microvascular complications were 0.54 (0.38, 0.78) and 0.55 (0.38, 0.80) for participants with serum 25(OH)D ≥50 nmol/L and major allele homozygotes (CC and AA), respectively, although no significant interaction was observed. CONCLUSIONS Higher serum 25(OH)D concentrations were significantly associated with lower risk of diabetic microvascular complications, including diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. Our findings suggest a potential beneficial role of maintaining adequate vitamin D status in the prevention of diabetic microvascular complications.
3D‐Printed Radiopaque Bioresorbable Stents to Improve Device Visualization
Authors: Yonghui Ding, Rao Fu, Caralyn Paige Collins, Sarah‐Fatime Yoda, Cheng Sun, Guillermo A. Ameer
Journal: Advanced Healthcare Materials (2022)

Bioresorbable stents (BRS) hold great promise for the treatment of many life-threatening luminal diseases. Tracking and monitoring of stents in vivo is critical for avoiding their malposition and inadequate expansion, which often leads to complications and stent failure. However, obtaining high X-ray visibility of polymeric BRS has been challenging because of their intrinsic radiolucency. This study demonstrates the use of photopolymerization-based 3D printing technique to fabricate radiopaque BRS by incorporating iodixanol, a clinical contrast agent, into a bioresorbable citrate-based polymer ink. The successful volumetric dispersion of the iodixanol through the 3D-printing process confers strong X-ray visibility of the produced BRS. Following in vitro degradation, the 3D-printed BRS embedded in chicken muscle maintains high X-ray visibility for at least 4 weeks. Importantly, the 3D-printed radiopaque BRS demonstrates good cytocompatibility and strong mechanical competence in crimping and expansion, which is essential for minimally invasive stent deployment. In addition, it is found that higher loading concentrations of iodixanol, e.g. 10 wt.%, results in more strut fractures in stent crimping and expansion. To conclude, this study introduces a facile strategy to fabricate radiopaque BRS through the incorporation of iodixanol in the 3D printing process, which could potentially increase the clinical success of BRS.